Sex Hormones and Rat Anterior Cruciate Ligament Strength

性激素与大鼠前十字韧带强度

• 批准号: 7686822
• 负责人: WILLIAM A ROMANI
• 金额: $ 8.07万
• 依托单位: MEDSTAR HEALTH RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686822
• 关键词: Acute; Anterior Cruciate Ligament; Athletic; Body Weight; Collagen; Collagen Fiber; Collagen Type III; Complex; Connective Tissue; Degenerative polyarthritis; Devices; Estradiol; Estrous Cycle; Exposure to; Failure; Female; Femur; Future; Gender; Genetic Transcription; Gonadal Steroid Hormones; Harvest; Hormonal; Hormones; Injury; Interdisciplinary Study; Life; Ligaments; Lower Extremity; Materials Testing; Measurable; Measures; Mechanics; Mediating; Messenger RNA; Military Personnel; Modeling; Operative Surgical Procedures; Physiological; Procollagen; Proteins; Rattus; Rehabilitation therapy; Relative (related person); Reporting; Research; Risk; Sprague-Dawley Rats; Tensile Strength; Testing; Testosterone; Testosterone Propionate; Time; Tissues; Trauma; Western Blotting; Woman; Women' s Group; Work; cost; design; human tissue; improved; in vivo; in vivo Model; injured; ligament injury; mRNA Expression; male; men; men' s group; novel strategies; premature; prevent; repaired; reproductive; research study; response; tibia

DESCRIPTION (provided by applicant): Women are between 2 and 10 times more likely to injure their anterior cruciate ligament (ACL) than men participating in similar military and athletic activities. Annual costs for surgical repair and rehabilitation of ACL injuries are over $850 million in females, alone. These expenses do not include the long-term costs related to the premature osteoarthritis (OA) that often follows the initial trauma. Gender specific differences in the hormonal milieu and response to specific steroid sex hormones have been suggested as potential causes for the disparities in ACL strength and injury risk between males and females. Most ACL injuries result from high tensile loads applied to the ligament during cutting and jumping. Type-I alpha-1 (T1C) and Type - 3 collagen (T3C) are the crucial structural components that define the ligament's ability to withstand tensile loads. If sex hormones influence ACL strength in a gender specific manner they must do so by mediating the mRNA transcription that regulates the T1C and T3C protein content essential to the ligament's mechanical strength. The mechanism and time course for sex hormones to modulate the collagen content and strength of the ACL is unknown. We hypothesize that steroid sex hormones mediate gender specific differences in the Type I and Type III collagen content and the mechanical strength of the ACL. To test this hypothesis the studies proposed in these specific aims will use a hydraulic materials testing device and Western blot analysis to measure ACL mechanical strength and collagen protein content in skeletally mature male and female rats injected with testosterone, estradiol or a combination of these hormones for 15 days. In our first specific aim the tensile strength of the ACL will be tested to demonstrate that sex hormones mediate gender specific changes in the strength of the ACL. Our second specific aim will clarify the mechanism by which sex hormones mediate changes in ligament strength by using Western blot analysis to demonstrate that selected steroid sex hormones mediate gender specific differences in T1C and T3C protein in the rat ACL. Accomplishing these aims will improve our understanding of the mechanism by which sex hormones influence collagen content and ACL strength and further explain the gender disparities in ACL injury rate. These findings are important as they will help direct future studies to identify women at risk for ACL injury and develop novel strategies to prevent their occurrence. This project is designed to determine the influence of selected steroid sex hormones on the collagen content and strength of the rat anterior cruciate ligament. It combines Western Blot analysis and materials testing in an in-vivo model. The proposed studies will improve our understanding of the mechanism by which sex hormones influence collagen content and ACL strength and further explain the gender disparities in ACL injury rate. These studies are important and they will help direct future studies to identify women at risk for ACL injury and develop novel strategies to prevent their occurrence.

描述（由申请人提供）：妇女受伤的前交叉韧带（ACL）的可能性比参加类似的军事和运动活动的男性高2到10倍。 ACL受伤的手术修复和康复的年度费用仅为女性超过8.5亿美元。这些费用不包括与通常遵循初始创伤的早产骨关节炎（OA）有关的长期费用。激素环境中的性别特定差异和对特定类固醇性激素的反应被认为是男性和女性ACL强度和伤害风险差异的潜在原因。大多数ACL损伤是由于在切割和跳跃过程中施加到韧带上的高拉伸负荷而造成的。 I型Alpha-1（T1C）和-3胶原蛋白（T3C）是定义韧带承受拉伸负荷的能力的关键结构成分。如果性激素以性别特定方式影响ACL强度，则必须通过介导调节韧带机械强度必不可少的T1C和T3C蛋白含量的mRNA转录来实现ACL强度。性激素调节ACL的胶原蛋白含量和强度的机制和时间过程是未知的。我们假设类固醇性激素介导了I型和III型胶原蛋白含量以及ACL的机械强度的性别特异性差异。为了检验这一假设，这些特定目标中提出的研究将使用液压材料测试装置和蛋白质印迹分析来测量ACL机械强度和胶原蛋白蛋白含量在骨骼成熟的雄性和雌性大鼠中注射睾丸激素，雌二醇或这些激素的组合15天。在我们的第一个特定目标中，将测试ACL的拉伸强度，以证明性激素介导了ACL强度的性别特定变化。我们的第二个特定目的将阐明性激素通过使用蛋白质印迹分析介导韧带强度的变化的机制，以证明选择的类固醇性激素介导了大鼠ACL中T1C和T3C蛋白的性别特异性差异。实现这些目标将提高我们对性激素影响胶原蛋白含量和ACL强度的机制的理解，并进一步解释ACL损伤率的性别差异。这些发现很重要，因为它们将帮助未来的研究确定有ACL损伤风险的妇女，并制定新的策略以防止其发生。该项目旨在确定选定的类固醇性激素对大鼠前交叉韧带的胶原蛋白含量和强度的影响。它将蛋白质印迹分析和材料测试结合在体内模型中。拟议的研究将提高我们对性激素影响胶原蛋白含量和ACL强度的机制的理解，并进一步解释ACL损伤率的性别差异。这些研究很重要，它们将帮助未来的研究确定有ACL损伤风险的妇女，并制定新的策略以防止其发生。